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01-09-2004 | Original Article

The INK4a/ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident

Authors: Alina Romanenko, Luisa Morell-Quadreny, Jose Antonio Lopez-Guerrero, Antonio Pellin, Valentin Nepomnyaschy, Alexander Vozianov, Antonio Llombart-Bosch

Published in: Virchows Archiv | Issue 3/2004

Abstract

Previous studies have shown that during the period subsequent to the Chernobyl accident, increases in morbidity, aggressivity and proliferative activity of renal-cell carcinomas (RCCs) in Ukrainian patients were recognized. The present paper describes the molecular alterations of those tumor suppressor genes located on chromosome 9p21 (INK4a/ARF locus and p15^INK4B) in 26 primary renal-cell epithelial tumors from patients with different degrees of radiation exposure after the Chernobyl accident in Ukraine. Radiometric measurement of Cesium 137 (¹³⁷Cs) was conducted with 1-day urine from all patients before surgery. Our results demonstrate that RCCs from patients living in the radio-contaminated areas showed aberrant hypermethylation of p14^ARF and p16^INK4A genes, associated with increased p38MAPK, p14^ARF, mdm2, cyclinD1 and Ki67 protein expression levels. Present findings show the possibility that chronic long-term low-dose radiation activates the INK4a/ARF locus, targeted by activation of the p38MAPK cascade. These actions could lead to disruptions and loss of cell cycle checkpoints and, thereby, to cellular transformation.

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Title: The INK4a/ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident
Authors: Alina Romanenko
Luisa Morell-Quadreny
Jose Antonio Lopez-Guerrero
Antonio Pellin
Valentin Nepomnyaschy
Alexander Vozianov
Antonio Llombart-Bosch
Publication date: 01-09-2004
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 3/2004
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-004-1056-7

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The INK4a/ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident

Abstract

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Abstract

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